Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight metabolites of retinol were isolated by high-performance liquid chromatography (HPLC) from the plasma of the non-human primate Macaca fascicularis after acute exposure to 150,000 IU of vitamin A per kilogram body weight. After enrichment and further chromatographic purification, the metabolites were reinjected individually into a second HPLC system which was connected on-line by a thermospray interface to a mass spectrometer operated in the positive ionization mode. Six retinoids were identified by (i) a comparison of their retention times with those of appropriate reference compounds in the two chromatographic systems and (ii) by comparison of their mass spectra with those of reference compounds. These retinoids were: 13-cis-4-oxoretinoic acid, all-trans-4-oxoretinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid, all-trans-retinoyl beta-glucuronide and all-trans-retinyl beta-glucuronide. One further metabolite could be identified for the first time as all-trans-4-oxoretinoyl beta-glucuronide by its mass spectrum and, after treatment of the unknown metabolite with beta-glucuronidase, by its hydrolysis product all-trans-4-oxoretinoic acid. The molecular structure of one metabolite could not be elucidated. A major metabolic pathway of high-dose vitamin A in the non-human primate is apparently the oxidation of the primary alcohol group of retinol resulting in the formation of all-trans-retinoic acid. Subsequently, a broad spectrum of various metabolites of all-trans-retinoic acid, including beta-glucuronides and retinoids with a 13-cis configuration, appear in the plasma.
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PMID:Characterization of oxidized and glucuronidated metabolites of retinol in monkey plasma by thermospray liquid chromatography/mass spectrometry. 240 Aug 53

Administration of a single oral dose (10 micrograms/kg) of tetrachlorodibenzo-p-dioxin (TCDD) caused a 33% decrease in retinyl esters in the livers of male rats, but a 13-fold increase in retinyl esters in the kidney and a 3-fold increase in serum retinol. Liver and kidney microsomal uridine diphosphoglucuronosyltransferase (UDPGT) activity toward all-trans-retinoic acid was increased 3.7- and 2.6-fold, respectively, ten days following exposure to TCDD. Verification of the in vitro formation of [3H]retinoyl beta-glucuronide (RG) was by cochromatography with authenic RG on reversed phase high pressure liquid chromatography (HPLC), identification of retinoic acid as the hydrolysis product after beta-glucuronidase treatment, and the characterization of the all-trans-retinoyl glucuronide by negative fragment mass spectroscopy, fast atom bobardment. We conclude that increased retinoic acid glucuronidation may be a contributing factor to the hepatic depletion of vitamin A and the increased excretion of vitamin A metabolites following TCDD exposure.
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PMID:Effect of tetrachlorodibenzo-p-dioxin (TCDD) on the glucuronidation of retinoic acid in the rat. 250 57

All-trans retinoyl fluoride reacts with the 3,6-lactone of glucuronic acid in slightly alkaline solution to give the lactone of retinoyl beta-glucuronide, along with other retinoyl glucurono-lactones, in about 60% yield. Hydrolysis of the lactone with very dilute alkali gives the free acid, retinoyl beta-glucuronide, in about 80% yield. Pure all-trans retinoyl beta-glucuronide (overall yield: 20-25%) was obtained free from other isomeric and anomeric forms by reverse-phase high pressure liquid chromatography. Retinoyl beta-glucuronide was characterized by UV-visible, infrared, and 1H-NMR spectra, by elementary analysis, by mass spectra, and by its susceptibility to hydrolysis by bacterial beta-glucuronidase.
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PMID:Chemical synthesis of all-trans retinoyl beta-glucuronide. 390 6

The effects of detergent, alamethicin (a channel-forming peptide), and the inducers phenobarbital and 3-methylcholanthrene on glucuronidation of all-trans-retinoic acid (atRA) and 5,6-epoxy-atRA have been investigated using liver microsomes from Sprague-Dawley and Fischer 344 rats. Conditions for enzymatic glucuronidation were optimized for substrate concentration, protein, and time by using atRA and Sprague-Dawley microsomes. With detergent-activated Sprague-Dawley microsomes, 5,6-epoxy-atRA was shown to be a significantly better substrate than atRA for microsomal glucuronidation (263 vs. 116 pmol/mg/min for 5,6-epoxy-atRA and atRA, respectively). The product of incubation of microsomes with atRA and UDP-glucuronic acid was identified as a glucuronide by beta-glucuronidase hydrolysis and by HPLC analysis. Alamethicin was shown to be a highly effective activator of glucuronidation activity; atRA and 5,6-epoxy-atRA glucuronidation rates were increased 2- and 3-fold, respectively, compared with detergent activation. Alamethicin (but not detergent) significantly increased retinoid glucuronidation by microsomes from Fischer 344 rats treated with phenobarbital and 3-methylcholanthrene, compared with untreated controls. The two compounds were equally effective inducers of activity, although 5,6-epoxy-atRA was again the better substrate. The same control and induced Fischer rat microsomes were photolabeled with [32P]5-azido-UDP-glucuronic acid in the absence or presence of detergent, two concentrations of alamethicin, and a 10-fold molar excess of unlabeled UDP-glucuronic acid. Photoincorporation into microsomal proteins from detergent-disrupted induced microsomes was 2-3 times greater than that of controls. Alamethicin increased photoincorporation of the probe into UDP-glucuronosyltransferase proteins an additional 1.5-2-fold in control and induced microsomes, compared with the respective detergent-activated samples.
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PMID:Glucuronidation of all-trans-retinoic acid and 5,6-epoxy-all-trans-retinoic acid. Activation of rat liver microsomal UDP-glucuronosyltransferase activity by alamethicin. 901 Jun 23